Class III β-Tubulin Isotype: A Key Cytoskeletal Protein at the Crossroads of Developmental Neurobiology and Tumor Neuropathology

Abstract

The expression of the cytoskeletal protein class III β-tubulin isotype is reviewed in the context of human central nervous system development and neoplasia. Compared to systemic organs and tissues, class III β-tubulin is abundant in the brain, where it is prominently expressed during fetal and postnatal development. As exemplified in cerebellar neurogenesis, the distribution of class III β-tubulin is neuron associated, exhibiting different temporospatial gradients in the neuronal progeny of the external granule layer versus the neuroepithelial germinal matrix of the velum medullare. However, transient expression of this protein is also present in the telencephalic subventricular zones comprising putative neuronal and/or glial precursor cells. This temporospatially restricted, potentially non-neuronal expression of class III β-tubulin may have implications in the accurate identification of presumptive neurons derived from transplanted embryonic stem cells. In the adult central nervous system, the distribution of class III β-tubulin is almost exclusively neuron specific. Altered patterns of expression are noted in brain tumors. In "embryonal"-type neuronal/neuroblastic tumors of the central nervous system, such as the medulloblastomas, class III β-tubulin expression is associated with neuronal differentiation and decreased cell proliferation. In contrast, the expression of class III β-tubulin in gliomas is associated with an ascending grade of histologic malignancy and with correspondingly high proliferative indices. Thus, class III β-tubulin expression in neuronal or neuroblastic tumors is differentiation dependent, whereas in glial tumors, it is aberrant and/or represents "dedifferentiation" associated with the acquisition of glial progenitor-like phenotype(s). From a diagnostic perspective, the detection of class III β-tubulin immunostaining in neoplastic cells should not be construed as categorical evidence of divergent neuronal differentiation in tumors, which are otherwise phenotypically glial. Because class III β-tubulin is present in neoplastic but not in normal differentiated glial cells, the elucidation of molecular mechanisms responsible for the altered expression of this isotype may provide critical insights into the dynamics of the microtubule cytoskeleton in the growth and progression of gliomas. (J Child Neurol 2003;18:851-866).